The enzyme c-Met is a receptor tyrosine kinase identified as a proto-oncogene and exhibits its physiological function when bound to HGF serving as a ligand. In normal tissues, c-Met plays a role in regeneration, wound healing, and organ formation. However, in many cancer cells (kidney cell cancer, stomach cancer, lung cancer, colorectal cancer, pancreatic cancer, ovarian cancer, liver cell cancer, head and neck cancer, melanoma, etc.), occurrence of over-expression, mutation, or translocation of c-Met is promoted, leading to an excessively activated state (Non-Patent Document 1). Under such conditions, c-Met plays a role in cell proliferation, infiltration/metastasis, tumorigenesis, neovascularization, and anti-apoptosis (see, Non-Patent Documents 2, 3, and 4). In addition, many studies have revealed that over-expression and elevation in activation level of c-Met in cancer cells are negatively correlated to prognosis, and c-Met is known to be a factor associated with a poor prognosis of cancer (see Non-Patent Documents 5 and 6).
Therefore, if a drug which specifically inhibits c-Met in cancer/tumor cells in which c-Met is activated through over-expression is administered, proliferation, infiltration, and metastasis of cancer cells would be inhibited more specifically and intensively, whereby the drug is expected to contribute to the treatment of cancer, prolongation of the life of patients, and enhancement in QOL. Meanwhile, in actual therapy, since the expression level and activation level of c-Met serve as indices for stratification of patients, the patients can receive appropriate therapy, which is highly preferred from an ethical viewpoint.
Hitherto, there has been widely studied use of acylthiourea compounds as pharmaceutical agents or other agents (see, for example, Patent Documents 1 to 7). However, there has never been reported the acylthiourea compound of the present invention represented by formula (I), the compound having an aminocarbonyl group serving as a 6-position substituent of the quinoline ring and an alkoxy group serving as a 7-position substituent of the quinoline ring.